title: Expression of BCR/ABL p210 from a knockin allele enhances bone marrow engraftment without inducing neoplasia.
abstract: Chronic myeloid leukemia (CML) and some acute lymphoblastic leukemias are characterized by the t(9;22) chromosome, which encodes the BCR/ABL oncogene. Multiple mouse models of CML express BCR/ABL at high levels from non-Bcr promoters, resulting in the development of leukemias. In contrast, a significant fraction of healthy humans have been found to have BCR/ABL-positive hematopoietic cells. To bridge the gap between the information derived from current mouse models and nonleukemic humans with the BCR/ABL oncogene, we generated a knockin model with BCR/ABL p210 expressed from the Bcr locus. Unlike previous models, expression of BCR/ABL from the knockin allele did not induce leukemia. BCR/ABL mutant cells did exhibit favorable bone marrow engraftment compared to control cells. These data suggest that BCR/ABL expression alone is insufficient to induce disease. This model allows for inducible spatial and temporal control of BCR/ABL expression for analysis of early steps in the pathogenesis of BCR/ABL-expressing leukemias.
authors.affiliation: Department of Internal Medicine and Cancer Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Samantha B
authors.initials: SB
authors.lastname: Foley
authors.forename: Zacariah L
authors.initials: ZL
authors.lastname: Hildenbrand
authors.forename: Abigail A
authors.initials: AA
authors.lastname: Soyombo
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Magee
authors.forename: Yipin
authors.initials: Y
authors.lastname: Wu
authors.forename: Katherine I
authors.initials: KI
authors.lastname: Oravecz-Wilson
authors.forename: Theodora S
authors.initials: TS
authors.lastname: Ross
mesh_terms: D000483:Alleles; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics*; D005786:Gene Expression Regulation; D055879:Gene Knock-In Techniques; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016044:Fusion Proteins, bcr-abl